U.S. patent application number 14/942447 was filed with the patent office on 2016-03-10 for therapeutic or prophylactic agent for corneal epithelium disorders and/or conjunctival epithelium disorders.
The applicant listed for this patent is KEIO UNIVERSITY, NIPPON SUISAN KAISHA, LTD., SCHOOL CORPORATION, AZABU VETERINARY MEDICINE EDUCATIONAL INSTITUTION. Invention is credited to Akiko HARAUMA, Fuminori KAWABATA, Tetsuya KAWAKITA, Toru MORIGUCHI, Kazuo TSUBOTA.
Application Number | 20160067204 14/942447 |
Document ID | / |
Family ID | 46084143 |
Filed Date | 2016-03-10 |
United States Patent
Application |
20160067204 |
Kind Code |
A1 |
HARAUMA; Akiko ; et
al. |
March 10, 2016 |
THERAPEUTIC OR PROPHYLACTIC AGENT FOR CORNEAL EPITHELIUM DISORDERS
AND/OR CONJUNCTIVAL EPITHELIUM DISORDERS
Abstract
The present invention provides an effective and safe
prophylactic and therapeutic pharmaceutical agent and supplement
for corneal epithelium disorders and/or conjunctival epithelial
disorders. This is a therapeutic and/or prophylactic agent for
corneal epithelium disorders and/or conjunctival epithelial
disorders comprising eicosapentaenoic acid and/or docosahexaenoic
acid, a glycerin ester or phospholipid comprising these fatty acids
as constituent fatty acids, or a lower alcohol ester of these fatty
acids as active ingredients. These preferably comprise EPA and/or
DHA in the form of a refined fish oil or refined krill oil. A total
of at least approximately 50 to 5,000 mg of EPA and/or DHA or the
esters thereof are taken daily, thereby easing corneal epithelium
disorders and/or conjunctival epithelial disorders. In addition,
the amount of tears may be recovered.
Inventors: |
HARAUMA; Akiko; (Tokyo,
JP) ; KAWABATA; Fuminori; (Tokyo, JP) ;
MORIGUCHI; Toru; (Kanagawa, JP) ; KAWAKITA;
Tetsuya; (Tokyo, JP) ; TSUBOTA; Kazuo; (Tokyo,
JP) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
NIPPON SUISAN KAISHA, LTD.
SCHOOL CORPORATION, AZABU VETERINARY MEDICINE EDUCATIONAL
INSTITUTION
KEIO UNIVERSITY |
Tokyo
Kanagawa
Tokyo |
|
JP
JP
JP |
|
|
Family ID: |
46084143 |
Appl. No.: |
14/942447 |
Filed: |
November 16, 2015 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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13885826 |
May 16, 2013 |
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PCT/JP2011/076643 |
Nov 18, 2011 |
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14942447 |
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Current U.S.
Class: |
514/560 |
Current CPC
Class: |
A61K 31/202 20130101;
A61K 9/0053 20130101; A61K 31/661 20130101; A61K 35/60 20130101;
A61P 27/02 20180101; A61K 31/232 20130101; A61P 27/14 20180101;
A61P 27/04 20180101; A61K 31/20 20130101; A61K 35/612 20130101;
A61P 43/00 20180101 |
International
Class: |
A61K 31/202 20060101
A61K031/202; A61K 31/20 20060101 A61K031/20; A61K 9/00 20060101
A61K009/00 |
Foreign Application Data
Date |
Code |
Application Number |
Nov 19, 2010 |
JP |
2010-258565 |
Claims
1-13. (canceled)
14. A method for reducing a dry eye symptom of a dry eye patient,
comprising orally administering to a dry eye patient having a dry
eye syndrome a composition in an amount effective to reduce the dry
eye symptom, wherein the composition comprises: eicosapentaenoic
acid in an amount of 28% or more; docosahexaenoic acid in amount of
12% or more; and n-6 type fatty acid in an amount in a range from 0
to 5%.
15. The method according to claims 14, wherein the dry eye syndrome
is decreased tear quantity, and the administration of the
composition increases the tear quantity.
16. The method according to claims 14, wherein the composition is
administered to the dry eye patient for at least four weeks
continuously.
17. The method according to claims 14, wherein the eicosapentaenoic
acid and the docosahexaenoic acid are present in the composition in
a form of eicosapentaenoic acid itself, docosahexaenoic acid
itself, esters of each of the eicosapentaenoic acid itself and the
docosahexaenoic acid itself, or mixtures thereof.
18. The method according to claims 14, wherein the composition is
in a form of refined fish oil or refined krill oil.
19. The method according to claims 14, wherein the composition
contains the eicosapentaenoic acid and the docosahexaenoic acid so
as to administer the eicosapentaenoic acid and the docosahexaenoic
acid in a range from approximately 50 to approximately 5,000 mg as
a total amount of eicosapentaenoic acid itself, docosahexaenoic
acid itself, and esters thereof, daily.
20. The method according to claims 14, wherein the composition
contains the eicosapentaenoic acid and the docosahexaenoic acid so
as to administer the eicosapentaenoic acid and the docosahexaenoic
acid in a range from approximately 300 to approximately 3,000 mg as
a total amount of eicosapentaenoic acid itself, docosahexaenoic
acid itself, and esters thereof, daily.
21. The method according to claims 14, wherein the composition
contains the eicosapentaenoic acid and the docosahexaenoic acid so
as to administer the eicosapentaenoic acid and the docosahexaenoic
acid in a range from approximately 900 to approximately 2,100 mg as
a total amount of eicosapentaenoic acid itself, docosahexaenoic
acid itself, and esters thereof, daily.
22. The method according to claims 14, wherein the composition
further comprises tocopherol as an antioxidant.
23. The method according to claims 17, wherein the esters of each
of the eicosapentaenoic acid and the docosahexaenoic acid are
glycerin esters thereof, phospholipid esters thereof, or lower
alcohol esters thereof.
Description
TECHNICAL FIELD
[0001] The present invention relates to the treatment and
prevention of eye diseases such as corneal epithelium disorders
and/or conjunctival epithelial disorders caused by irritation due
to dry eyes, contact lenses, and eyelashes inverted towards the
eyelids, conjunctival lithiasis, viral conjunctivitis, and allergic
conjunctivitis.
BACKGROUND ART
[0002] Along with the spread of personal computers, cell phones,
and the like, the number of people suffering from eyestrain or
feeling some kind of discomfort in their eyes is on the rise.
Particularly, regarding contact lens users, complaints of
discomfort such as dryness of the eyes, and gritty sensations
caused by staring at the screen are increasing. Dryness of the
eyes, that is, dry eye is attracting attention as the cause of said
symptoms.
[0003] Dry eye is a disease in which a disorder is generated on the
eye surface due to a decrease or qualitative change in tears,
thereby causing the eyes to become dry and prone to damage due to
declined amount of tears, and making the use of contact lenses
difficult.
[0004] According to the diagnostic criteria for dry eye by the Dry
Eye Society in 2006, dry eye is diagnosed when all three of:
subjective symptoms (evaluation of pain and dryness by a VAS test);
abnormal tear fluid (evaluation from tear film breakup time or
Schirmer's test); and corneal as well as conjunctival disorders
(evaluation by fluorescein or rose bengal staining) are confirmed,
with dry eye suspected when two of these are confirmed.
[0005] Saline eye drops and Viscous eye drops such as chondroitin
sulfate are used as symptomatic treatments against dry eye.
Moreover, one treatment involves closing the tear outlet in order
to retain tears on the eye surface for as long as possible.
[0006] Fine scratches generated on the corneal epithelium and/or
conjunctival epithelium due to irritation due to contact lenses and
eyelashes inverted towards the eyelids, conjunctival lithiasis,
viral conjunctivitis, allergic conjunctivitis, and the like are
also possible in addition to dry eye.
[0007] Nutritional supplements for dry eye involving the
concomitant use of GLA-rich flaxseed oil, eicosapentaenoic acid
(hereinafter, referred to as EPA) and/or docosahexaenoic acid
(hereinafter, referred to as DHA) are described in Patent Document
1. The effect of essential fatty acids with respect to dry eye is
described in Non-patent Document 1.
BACKGROUND ART DOCUMENTS
Patent Documents
[0008] Patent Document 1: Japanese Unexamined Patent Application
Publication (Translation of PCT Application) No. 2005-535733
Non-Patent Documents
[0009] Non-patent Document 1: "Essential Fatty Acids in the
Treatment of Dry Eye," The Ocular Surface, 8 (1) p18-28, 2010.
SUMMARY OF THE INVENTION
Problems to be Solved by the Invention
[0010] Even when not serious, dry eye impairs the comfort of daily
life. An object of the present invention is to investigate the
cause of dry eye and provide a safe therapeutic strategy without
the worry of side effects that are not symptomatic treatments.
Means for Solving the Problems
[0011] In advancing studies on n-3 fatty acid-deficient mice, the
inventors of the present invention found that the amount of tears
in n-3 fatty acid-deficient mice declined, hypothesizing that n-3
fatty acid was involved in the amount of tears. Furthermore, they
found that said amount of tears may be brought back to normal
levels by administrating refined fish oil with high EPA and DHA
content, which are n-3 fatty acids, to the n-3 fatty acid-deficient
mice, thereby completing the present invention.
[0012] The present invention is summarized by the therapeutic
and/or prophylactic agent for corneal epithelium disorders and/or
conjunctival epithelial disorders of (1) to (7) and the tear
quantity restorative agent of (8) to (13).
[0013] (1) A therapeutic and/or prophylactic agent for corneal
epithelium disorders and/or conjunctival epithelial disorders,
comprising EPA and/or DHA or esters thereof as an active
ingredient.
[0014] (2) The therapeutic and/or prophylactic agent according to
(1), wherein said corneal epithelium disorders and/or conjunctival
epithelial disorders are disorders caused by any from the group
consisting of: irritation due to dry eyes, contact lenses, and
eyelashes inverted towards the eyelids, conjunctival lithiasis,
viral conjunctivitis, and allergic conjunctivitis.
[0015] (3) The therapeutic and/or prophylactic agent according to
(1) or (2), wherein the esters of EPA and/or DHA are comprised in
the form of a glycerin ester, lower alcohol ester, phosphate ester
or refined fish oil.
[0016] (4) The therapeutic and/or prophylactic agent according to
any one of (1) to (3), for the purpose of ingesting a total of at
least approximately 50 to 5,000 mg of eicosapentaenoic acid and/or
docosahexaenoic acid or esters thereof daily.
[0017] (5) The therapeutic and/or prophylactic agent according to
any one of (1) to (3), for the purpose of ingesting a total of at
least approximately 300 to 3,000 mg of EPA and/or DHA or esters
thereof daily. (6) The therapeutic and/or prophylactic agent
according to any one of (1) to (3), for the purpose of ingesting a
total of at least approximately 1,000 to 2,000 mg of EPA and/or DHA
or esters thereof daily.
[0018] (7) The therapeutic and/or prophylactic agent according to
any one of (1) to (6), further comprising tocopherol as an
antioxidant.
[0019] (8) A tear quantity restorative agent comprising EPA and/or
DHA or ethers thereof as an active ingredient.
[0020] (9) The tear quantity restorative agent according to (8),
wherein the esters of EPA and/or DHA are comprised in the form of a
glycerin ester, lower alcohol ester, phosphate ester, or refined
fish oil.
[0021] (10) The tear quantity restorative agent according to (8) or
(9), for the purpose of ingesting a total of at least approximately
50 to 5,000 mg of eicosapentaenoic acid and/or docosahexaenoic acid
or esters thereof daily.
[0022] (11) The tear quantity restorative agent according to (8) or
(9), for the purpose of ingesting a total of at least approximately
300 to 3,000 mg of EPA and/or DHA or esters thereof daily.
[0023] (12) The tear quantity restorative agent according to (8) or
(9), for the purpose of ingesting a total of at least approximately
900 to 2,100 mg of EPA and/or DHA or esters thereof daily.
[0024] (13) The tear quantity restorative agent according to any
one of (8) to (12), further comprising tocopherol as an
antioxidant.
Advantage of the Invention
[0025] Corneal epithelium disorders and/or conjunctival epithelial
disorders caused by irritation due to dry eyes, contact lenses, and
eyelashes inverted towards the eyelids, conjunctival lithiasis,
viral conjunctivitis, allergic conjunctivitis, and the like may be
treated or prevented by administrating EPA and DHA, which are n-3
fatty acids. EPA and DHA are capable of increasing the amount of
tears, thereby easing said symptoms. Thus, a pharmaceutical agent,
supplement, and the like capable of improving symptoms such as dry
eye in the form of refined fish oil with a long dietary history and
no worry of side effects may be provided.
BRIEF DESCRIPTION OF THE DRAWINGS
[0026] FIG. 1 is a drawing showing the results from evaluating the
subjective evaluation of eye pain using a VAS test. In the drawing,
*P<0.05, #P<0.1 indicates the significant difference
according to a Mann-Whitney U test.
[0027] FIG. 2 is a drawing showing the results from evaluating eye
dryness using a VAS test.
[0028] FIG. 3 is a drawing showing the results from measuring the
tear film breakup time. n=24 or 30. In the drawing, *P<0.05,
#P<0.1 indicates the significant difference according to a
Mann-Whitney U test.
[0029] FIG. 4 is a drawing showing the results from evaluating
scratches on the eye using fluorescein staining. n=24 or 30.
[0030] FIG. 5 is a drawing showing the variation of FIG. 4.
[0031] FIG. 6 is a drawing showing the results from evaluating
scratches on the eye using rose bengal staining. n=24 or 30.
[0032] FIG. 7 is a drawing showing the variation of FIG. 6. In the
drawing, *P<0.05 indicates the significant difference according
to a Mann-Whitney U test. In the drawing, **P<0.05 indicates the
significant difference according to two-way ANOVA.
[0033] FIG. 8 is a drawing showing the results from evaluating the
amount of tears using a Schirmer's test. n=24 or 30.
MODE FOR CARRYING OUT THE INVENTION
[0034] The present invention is a prophylactic or therapeutic agent
for corneal epithelium disorders and/or conjunctival epithelial
disorders, comprising EPA and/or DHA or esters thereof as an active
ingredient. Although several reports exist in which n-6 type fatty
acids such as flaxseed oil are used as treatments for dry eye, it
is unknown how the single ingestion of n-3 fatty acids (especially
EPA and DHA) affect corneal epithelium disorders and/or
conjunctival epithelial disorders.
[0035] The inventors of the present invention found that a lack of
n-3 fatty acid evidently decreases the amount of tears and
confirmed that said amount of tears is recovered by the ingestion
of refined fish oil comprising EPA and DHA.
[0036] The EPA and/or DHA used in the present invention is
preferably an ester with a glycerol, that is, triglyceride,
diglyceride, monoglyceride, or phospholipid, that is,
phosphatidylcholine, phosphatidylserine, phosphatidyl ethanolamine,
phosphatidylinositol, phosphatidylglycerol, cardiolipin,
phosphatidic acid (all comprising lysozymes body), or esters with
lower alcohol (carbon number: 1 to 5), that is, methyl ester, ethyl
ester, and the like. Those with n-3 fatty acids such as EPA, and
DHA as the main constituent, which do not substantially contain n-6
type fatty acids, are preferable. Specifically, the total amount of
n-6 type fatty acid is preferably 10% by weight or less and more
preferably 5% by weight or less.
[0037] Specifically, refined fish oil, concentrated oil (oil with
the EPA and DHA of refined fish oil concentrated by enzyme
reactions or chemical reactions), and the like may be used as a
triglyceride. Moreover, krill oil, and the like may be used as a
phospholipid. Sources of n-3 polyunsaturated fatty acid comprising
EPA and DHA include: fish or shellfish extract, animal extract, egg
yolk extract, plant extract, fungi extract, and the like,
preferably krill oil, fish oil, fish extract, squid extract, bonito
ovary extract, extracts from genetically modified plants, extracts
from labyrinthulea, and the like. Krill oil, squid extract, and
bonito ovary extract are substances with high phospholipid content.
By means of techniques involving concentrating, extracting, and/or
refining, mixing, and the like that are generally known in
technical fields, the phospholipid concentration and purity of said
substances may be adjusted as required.
[0038] EPA and/or DHA are known to be effective for hyperlipidemia
and allergy symptoms, with many pharmaceutical agents and various
supplements already commercially available. A capsule form similar
to these may be used for the purpose of the present invention.
Moreover, it is possible to ingest these by adding them to various
beverages and food products.
[0039] Specifically, gelatin capsules processed from oils and fat
with antioxidants added to refined fish oil are often used.
[0040] The refined fish oil may be fish oil from any fish as long
as said fish oil contains EPA and DHA. Examples of fish oil with
high EPA content include sardine oil, cod liver oil, and the like,
while examples of fish oil with high DHA content include tuna oil,
bonito oil, and the like.
[0041] Concentrated EPA/DHA oil refers to fats or oils with
increased EPA/DHA concentrations in the triglyceride of refined
fish oil using lipase, and the like due to regioselectivity and
fatty acid selectivity (refer to Japanese Examined Patent
Application Publication No. H4-16519).
[0042] The therapeutic and/or prophylactic agent of the present
invention is orally administered to patients with dry eye symptoms
with a total quantity of EPA and/or DHA or ester thereof of
approximately 50 to 5,000 mg, preferably 300 to 3,000 mg, more
preferably approximately 900 to 2,100 mg, and most preferably 1,100
to 1,900 mg daily either at once or by dividing the dosage. Effects
are observed upon continuous administration for at least 4
weeks.
[0043] EPA and/or DHA have a long history of usage with other
methods, so there are believed to be no problems with regards to
safety.
[0044] Anthocyanidin, lutein, eye bright, acer maximowiczianum,
vitamins, and the like, which have been determined as favorable for
recovery from eye fatigue, may be added to the therapeutic and/or
prophylactic agent for corneal epithelium disorders and/or
conjunctival epithelial disorders or the tear quantity restorative
agent of the present invention.
[0045] The present invention will now be explained in greater
detail through the use of working examples, but is in no way
limited to these working examples.
Working Example 1
Creating an n-3 Fatty Acid-Deficient Animal
[0046] Experimental animal feeds generally comprise n-3 fatty acid
with an appropriate DHA content; therefore, in order to create an
n-3 fatty acid-deficient animal, a special feed that does not
contain n-3 fatty acid must be used. Furthermore, normally raised
animals receive sufficient DHA ingestion from the placenta and the
dam's breast milk from prior to birth to the weaning period, so it
is no simple matter to create a target n-3 fatty acid-deficient
animal over a single generation. Taking these facts into
consideration, an n-3 fatty acid-deficient feed (n-3 Def, linolenic
acid, 14.4%; .alpha.-linolenic acid, 0.1%) comprising 7% fat and
oil was prepared with AIN93G (standard refined feed composition for
nutrition research of mice and rats presented by the American
Institute of Nutrition) as the basal feed. The n-3 fatty acid (n-3
Adq, linolenic acid, 14.3%; .alpha.-linolenic acid, 2.6%)
containing .alpha.-linolenic acid (18:3, n-3) was used as the
normal feed. These feeds were fed to female mice immediately
following weaning (3 weeks old), which were then raised;
subsequently, the mice were crossbred after maturing to obtain
second generation mice, and said second generation male mice, aged
11 months old, were used for the experiment. Moreover, in order to
avoid any effects from the dam upon conducting the experiment, the
test was set such that the samples in each group all had different
mothers.
Preparing the Test Drug
[0047] Fish oil (refined fish oil EPA-28 (containing 28% or more of
EPA and 12% or more of DHA) manufactured by Nippon Suisan Kaisha,
Ltd.) was used as the test drug, and the dosage was adjusted such
that the DHA content became 5 mg/head and the EPA content became 11
mg/head. Palm oil was used in the control group, which was prepared
such that it had the equivalent fatty acid content of the fish oil
group. The principal fatty acid composition of fish oil is shown in
Table 1 (the n-6 type fatty acid content of 18:2 was 1.1% and 20:4
was 1.3%).
TABLE-US-00001 TABLE 1 Fatty acid (%) 14:0 4.9 16:0 6.2 16:1 8.7
16:4 4.8 18:1 8.3 18:4 5.1 20:5 (EPA) 29.1 22:6 (DHA) 15.0
Operation Procedure
[0048] A phenol red thread (Zone-Quick, SHOWA YAKUHIN KAKO CO.,
LTD.) for checking the amount of tear fluid was used to measure the
amount of tears (the length at which the thread indicates a red
color) secreted within 30 seconds in n-3 Def and n-3 Adq mice.
These mice were divided into two groups and each group was orally
administered fish oil or palm oil-mixed feed for 7 days;
subsequently, the amount of tear fluid was measured again on day 8,
and on day 9, the retina related to the vision and the lachrymal
gland and the meibomian gland related to the secretion of tear
fluids were sampled and the fatty acid composition was
measured.
Experimental Results and Discussion
[0049] Tear fluids are configured from a lipid layer secreted from
the meibomian gland, an aqueous layer secreted from the lachrymal
gland, and a mucus layer secreted from the conjunctiva in order,
with the layers contacting the exterior being first. Dry eye is
also referred to as corneal xerosis and is an eye disease in which
scratches and disorders are generated due to the surface of the
eyeballs drying, accompanied by eye discomfort and impaired visual
function; wherein, a tear deficient dry eye in which the tear fluid
of the aqueous layer secreted from the lachrymal gland declines,
and an evaporative dry eye caused due to insufficient lipid layer
secreted from the meibomian gland are known.
[0050] A clear decline was exhibited in the amount of tear fluid in
elderly n-3 fatty acid-deficient mice, suggesting the exhibition of
dry eye symptoms (Table 2). The fish oil group in which fish oil
was administered to said n-3 fatty acid-deficient mice for 7 days
was observed to exhibit a significant increase in the amount of
tears compared to the control group (recovered amount of tears)
(Table 3). Moreover, because said amount of tears was almost the
same as that of normal mice, it was believed that the amount of
tears had almost completely recovered. From the results of the
fatty acid composition of the EPA and DHA of organs involved with
the amount of tears, an increase was observed in both the lachrymal
gland and meibomian gland due to fish oil administration (Table
4).
[0051] From the results above, it became clarified that n-3 fatty
acid-deficient animals exhibit evident dry eye symptoms, and that
said symptoms recover due to the ingestion of fish oil. Moreover,
from the reaction results of the fatty acid composition following
fish oil administration, it was believed that the dry eye symptoms
of n-3 fatty acid-deficient animals were caused by the decreased
amount of tear fluid secretion due to decreased functioning of both
or either of the lachrymal gland and meibomian gland.
TABLE-US-00002 TABLE 2 Amount of tear fluid (mm) Number of animals
(Mean .+-. SEM) n-3 Adq mice 18 9.64 .+-. 0.79 (normal mice) n-3
Def mice 17 5.91 .+-. 0.59** (**P < 0.01, t-test)
TABLE-US-00003 TABLE 3 n-3 fatty acid-deficient Normal mice mice
Control group Fish oil group Control group Fish oil group (n = 8)
(n = 10) (n = 9) (n = 8) Amount of tears (mm) 11.97 .+-. 1.69 11.71
.+-. 1.98 7.07 .+-. 0.89 11.75 .+-. 2.11* (*P < 0.05, vs Control
group, t-test)
TABLE-US-00004 TABLE 4 Fatty acid composition of the main
organization (percentage with respect to the total fatty acid, %)
Normal mice n-3 fatty acid-deficient mice Control group Fish oil
group Control group Fish oil group (n = 8) (n = 10) (n = 9) (n = 8)
Retina EPA 0.29 .+-. 0.02 0.44 .+-. 0.03** 0.02 .+-. 0.01 0.02 .+-.
0.02** DHA 25.25 .+-. 0.55 25.87 .+-. 0.70 15.79 .+-. 1.03 20.50
.+-. 0.75** Lachrymal EPA 0.88 .+-. 0.09 1.41 .+-. 0.12** 0.12 .+-.
0.01 0.65 .+-. 0.05** gland DHA 10.07 .+-. 0.61 10.42 .+-. 0.57
2.05 .+-. 0.19 3.25 .+-. 0.28** Meibomian EPA 0.12 .+-. 0.01 0.19
.+-. 0.01** 0.08 .+-. 0.005 0.17 .+-. 0.01** gland DHA 1.60 .+-.
0.09 2.10 .+-. 0.06** 0.25 .+-. 0.01 1.28 .+-. 0.13** (**P <
0.01, vs Control group, t-test)
Working Example 2
[0052] Using the same fish oil (refined fish oil EPA-28 (containing
28% or more of EPA and 12% or more of DHA) manufactured by Nippon
Suisan Kaisha, Ltd.) as in Working Example 1, the effect on human
corneal epithelium disorders was confirmed.
Abstract of the Test Protocol
[0053] The efficacy of EPA and DHA was evaluated using a
double-blind test with respect to the 27 cases of subjects
diagnosed with dry eye from the diagnostic criteria for dry eyes
(2006, Dry Eye Society). Active or placebo supplements were taken
for 12 weeks while continuing normal dry eye treatment using eye
drops, and the like. Capsules of refined fish oil (15 capsules)
were administered to the active group for the purpose of ingesting
1,245 mg of EPA and 540 mg of DHA daily. Capsules of medium chain
triglyceride (MCT) (15 capsules) were administered to the placebo
group. The efficacy was measured a total of 5 times: prior to
administration; week 4, week 8, and week 12 following
administration; and week 4 of the follow-up period subsequent to
administration.
[0054] The following 6 items were evaluated: [0055] Subjective
evaluation of eye pain by the VAS test: the degree of pain was
visually evaluated using a visual analog scale. [0056] Subjective
evaluation of dryness of the eyes by the VAS test: the degree of
dryness was visually evaluated using a visual analog scale. [0057]
Tear film breakup time (BUT, tear film breakup time): one of the
diagnostic criteria for dry eye. In this test, subjects are asked
to cease blinking after fluorescein is instilled, after which the
time until the tear film of the corneal surface ruptures is
measured. The retention of tear fluid is measured. 10 seconds or
more is evaluated as being normal, with 5 seconds or less evaluated
as being suspicious of dry eye. [0058] Evaluation of scratches on
the eyes using fluorescein staining: a yellow staining liquid
called fluorescein is instilled to stain scratches on the eye
surface in order to evaluate the seriousness of dry eye. The
fluorescein also stains the conjunctiva, but it mainly allows the
evaluation of scratches on the cornea. [0059] Evaluation of
scratches on the eyes using rose bengal staining: a red staining
liquid called rose bengal is instilled to stain scratches on the
eye surface in order to evaluate the seriousness of dry eye. Rose
bengal mainly allows the evaluation of the conjunctiva with an
impaired mucus layer. [0060] Evaluation of the amount of tears
using Schirmer's test: Schirmer's test is a test for measuring the
amount of tear fluid secretion, involving sandwiching a long and
narrow filter paper on the lower eyelids for 5 minutes and
measuring the length of wetness from tears. 5 mm or less is
evaluated as an abnormal value.
Results
[0061] The number of subjects was 12 in the active group and 15 in
the placebo group.
[0062] The results of each evaluation item are shown in FIGS. 1 to
8.
[0063] It was found that there was an effect with a statistical
difference compared to the placebo group regarding the evaluation
of eye pain by the VAS test, tear film breakup time, and the rose
bengal staining test. In other evaluations as well, a tendency was
observed in which the results were more favorable in the active
group compared to the placebo group.
Working Example 3
[0064] The effect was compared between the active group that took
162 mg of EPA, 784 mg of DHA, 59 mg of anthocyanidin, and 17 mg of
lutein daily in the form of a capsule and the placebo group that
took capsules comprising the medium chain triglyceride using a
double-blind randomized comparative test targeting patients having
eye strain symptoms.
Result
[0065] The number of subjects was 11 in the active group and 9 in
the placebo group. Upon a subjective symptom evaluation at week 4
following the commencement of administration, a statistically
significant improvement in terms of dryness from among the eye
symptoms was observed in the active group compared to the placebo
group. Moreover, from among the eye symptoms, significant
improvement in the feeling of fatigue, flickering, bloodshot eyes,
and dimness of sight was observed in the active group at week 4
following the commencement of administration compared to prior to
administration.
INDUSTRIAL APPLICABILITY
[0066] The present invention can provide the pharmaceutical agent
and supplement for easing eye disorders, especially corneal
epithelium disorders and conjunctival epithelium disorders due to
various causes such as irritation due to dry eye, use of contact
lenses, and eyelashes inverted towards the eyelids, conjunctival
lithiasis, viral conjunctivitis, and allergic conjunctivitis, and
improving the feeling of discomfort, and the like.
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